FIELD OF THE INVENTION
[0001] The present invention relates to a nutritional product for HIV patients. More specifically
the invention relates to a nutritional composition that provides carefully selected
nutritional ingredients specifically supporting HIV patients with nutritionally related
symptoms. This invention also relates to the manufacture of a nutritional supplement
for use in HIV patients.
BACKGROUND OF THE INVENTION
[0002] Infections with the human immunodeficiency virus (HIV) and the development of acquired
immunodeficiency syndrome (AIDS) have had a significant impact on domestic and global
health, social, political, and economic outcomes. Worldwide, the number of HIV-1 infected
persons exceeds 40 million, the majority of whom live in Asia, sub-Saharan Africa
and South America. Despite all the therapeutic advantages achieved during the last
decade, including the development of highly active antiretroviral therapy ("HAART"),
once an individual has become infected, eradication of the virus still remains impossible.
[0003] The importance of nutritional support of HIV infected persons is recognized nowadays.
Infected patients may have increased needs for basal energy, proteins, and micronutrients
due to the metabolic stress they experience. This stress, coupled with the anorexia
and mal-absorption associated with the disease, promotes malnutrition. Malnutrition
generally affects e.g. the immune-competence, (work) performance and cognition. Providing
extra nutrition helps these patients to improve their general nutritional status.
[0004] Currently several products are on the market for nutritional support of HIV patients.
Different commercial suppliers have several clinical nutrition products on the market,
which are listed below.
- 1. Advera, Ross Abbott
Caloric Distribution:
Protein: 18.7% (Soy protein hydrolysate, Sodium Caseinate)
Carbohydrate: 65.5% (maltodextrin, sucrose, soy fiber)
Fat: 15.8% (Canola, MCT, Refined, deodorized sardine oil 1.5 e%)
Caloric Density: 1.28 kcal/mL
- 2. Resource, Novartis
Caloric Distribution:
Protein: 14% (Sodium and Calcium Caseinates, Soy Protein Isolate)
Carbohydrate: 64% (Corn Syrup, Sugar)
Fat: 22% (High Oleic Sunflower Oil, Corn Oil)
Caloric Density: 1.06 kcal/mL
- 3. Benecalorie, Novartis
Caloric Distribution:
Protein: 9% (Calcium Caseinate)
Carbohydrate: 0%
Fat: 91% (High Oleic Sunflower Oil, Mono and Diglycerides)
Caloric Density: 7 kcal/mL
- 4. Boost, Mead Johnson now product sold by Novartis
Caloric Distribution:
Protein: 24% (milk protein concentrate, Ca & Na caseinates)
Carbohydrate: 55% (corn syrup solids, sugar)
Fat: 21% (canola, high oleic sunflower and corn oils)
Caloric Density: 1.01 kcal/mL
[0005] However, despite the availability of products which support the general nutritional
requirements of HIV infected patients, there are no nutritional products available
which do not only improve the nutritional status but which additionally significantly
reduce or prevent specific HIV infection related symptoms, in particular immune dysfunction,
intestinal dysfunction and/or glutathione status of the subjects.
SUMMARY OF THE INVENTION
[0006] The current nutritional treatments of HIV patients have the disadvantage that these
do not give an overall solution for all the nutritionally related medical problems
of HIV patients, in particular infection related immune dysfunction, intestinal dysfunction
and/or glutathione status. In one embodiment the present invention relates to the
use of oligosaccharides and cysteine and/or source of cysteine in the manufacture
of a composition for use in a method for the treatment of HIV or AIDS, said method
comprising administering to a mammal a composition comprising a therapeutically effective
amount of oligosaccharide and cysteine and/or source of cysteine, and wherein the
cysteine and/or source of cysteine provide at least 100 mg cysteine equivalent in
a daily dose. In another embodiment the compositions further comprise one or more
polyunsaturated fatty acids- (PUFAs) and/or one or more biologically active compounds,
in particular milk-derived compounds.
[0007] The present invention provides complete nutritional supplements suitable for the
nutritional treatment of HIV patients. The nutritional supplements of the present
invention comprise at least 2, preferably at least 3 components supporting the subject's
gut function, glutathione (GSH) status and/or immune function. It was surprisingly
found that, by carefully choosing combinations of nutritional ingredients, several
nutrition-related side effects of the HIV infection (i.e. infection related symptoms)
can be prevented and/or significantly reduced. The effect was found to be much better
when several disease related symptoms were targeted at the same time than when the
patient was given only one of the individual ingredients as has been practiced until
today.
[0008] A healthy gut and healthy gut flora are intricately linked to healthy immune function.
Potential immune modulating effects by specific fibers/oligosaccharides may be the
indirect result of the influence on the gut flora composition (immune effects of bifidobacteria
and lactobacilli types have been documented) and/or function (fermentation of fibers
produces compounds such as short chain fatty acids that influence general and immunological
function of gut cells). Surprisingly the inventors found that the DC-SIGN molecule
of dendritic cells can be blocked by certain oligosaccharides. As the blockage of
this molecule can potentially prevent the transmission of HIV, the use of these oligosaccharides
for blocking the DC-SIGN receptor and for the manufacture of compositions for the
prophylaxis and/or treatment of DC-SIGN mediated diseases (in particular HIV and AIDS)
is provided in one embodiment of the invention.
DETAILED DESCRIPTION
General definitions
[0009] "Oligosaccharides" refers to carbohydrate chains of monosaccharide units with a chain
length of between 1 and 5000, more preferably between 2 and 250, more preferably between
2 and 50, most preferably between 2 and 10.
[0010] "Degree of polymerization" or "DP" refers to the total number of saccharide units
in an oligosaccharide chain. The "average DP" refers to the average DP of oligosaccharide
chains in a composition, without taking possible mono- or disaccharides into account
(which are preferably removed if present). The average DP of a composition is used
to distinguish between compositions. Preferably the average degree of polymerization
of oligosaccharide mixtures is between 2 and 100, more preferably between 3 and 250,
e.g. between 3 and 50.
[0011] "Co-administration" of two or more substances refers to the administration of these
substances to one individual, either in one composition or in separate compositions
(kit of parts; as a combined composition), which are administered at the same time
(simultaneously) or within a short time-span (separate or sequential use, e.g. within
minutes or hours).
[0012] The term "comprising" is to be interpreted as specifying the presence of the stated
parts, steps or components, but does not exclude the presence of one or more additional
parts, steps or components.
[0013] "Percentage" or "average" generally refers to percentages of averages by weight,
unless otherwise specified or unless it is clear that another basis is meant.
[0014] "GOS" or "galactooligosaccharides", or "trans-galactooligosaccharides" or "TOS" refers
to oligosaccharides composed of galactose units.
[0015] "Treatment of HIV" refers to the significant reduction of one or more of HIV infection
related symptoms/dysfunctions selected from immune dysfunction, intestinal dysfunction
and/or low glutathione status. In one embodiment treatment of HIV refers to a significant
reduction in the spread of HIV due to blockage of the DC-SIGN receptor, as will be
clear from the context.
[0016] A "significant reduction" refers to a reduction of the symptom (or spread of HIV)
by at least 5%, 10%, 15%, 30%, 50% or even 100% compared to control subjects, not
being administered the compositions according to the invention. The symptoms can be
measured as known in the art, e.g. immune dysfunction can be assessed by measuring
CD4
+ cell counts. Blockage of the DC-SIGN receptor can be determined as in Example 1.
[0017] The object of the present invention is to provide nutritional compositions suitable
for treating HIV patients in order to improve their nutritional status and at least
two, preferably at least three HIV related symptoms. The compositions according to
the invention are particularly useful for patients with a CD4
+ T cell count that is below the critical level of around 700 cells/µl blood, when
generally HAART therapy is not yet needed, but when patients do already develop or
experience one or more of the immure-, intestinal- and/or glutathione related dysfunctions.
[0018] Thus, the present compositions are suitable for treatment of one or more of HIV infection
related dysfunctions, in particular:
- 1. immune dysfunction, i.e. a decrease in CD4+ T cell count leading to impaired immune function;
- 2. intestinal dysfunction, i.e. intestinal problems, specifically HIV induced malabsorption
and diarrhea; and/or
- 3. low glutathione status, specifically low glutathione levels in the blood and intracellularly
in the T cells.
[0019] In a preferred embodiment the compositions are suitable for treatment of at least
immune dysfunction and low glutathione status. These compositions comprise suitable
amounts of both oligosaccharides and cysteine and/or source of cysteine. The compositions
further comprise at least 25 en% of a fat blend comprising n-3 and n-6 fatty acids
and optionally one or more biologically active compounds and are suitable for treatment
of all three of the above dysfunctions.
[0020] Since CD4
+ T-lymphocytes are infected and destroyed by HIV, the progression of HIV can be routinely
and regularly monitored by measuring the CD4
+ T-lymphocyte count in the circulation. The initial period after infection with HIV,
which can last from three to more than ten years, is characterized by a slow but gradual
decline in total CD4
+ T-cell counts, with no apparent symptoms of decreased resistance to infections. The
first signs of infectious complications usually occur when CD4
+ T cell counts are below 700 cells /µl blood. At this point, the HIV seropositive
individual may experience respiratory (coughs, colds, flu) and/or gastrointestinal
(bowel discomfort, diarrhea) symptoms. These symptoms are still relatively mild and
may be considered sub clinical; although bothersome to the individual, they are usually
not sufficiently severe to cause hospitalization or the initiation of highly active
antiretroviral treatment (HAART).
[0021] One of the cell types first encountered by human immunodeficiency virus type 1 (HIV-1)
following sexual transmission is dendritic cells (DC). DC capture HIV-1 through C-type
lectin receptors, of which the best-studied example is DC-SIGN, which mediates HIV-1
internalization. DC can keep the virus infectious for several days and are able to
transmit HIV-1 to CD4(+) T cells. As is described in Example 1, the present inventors
surprisingly found that oligosaccharides can binds to DC-SIGN.
Compositions and uses according to the invention
[0022] The compositions according to the invention are suitable for the treatment of HIV
and/or AIDS in a mammalian subject. The subjects are preferably human subjects infected
with HIV and comprising a CD4
+ cell count of about 700 cell per µl blood or less, more preferably between about
200 and 700 cells per µl, e.g. between about 200 and 500 cells or between about 200
and 600 or 500 and 700 cells per µl blood. In one embodiment the subjects have a CD4+
cell count of 700 or less but are not on highly active antiretroviral therapy (HAART),
[0023] In one embodiment the nutritional compositions are preferably food supplements and
comprise oligosaccharides and cysteine and/or source of cysteine.
Oligosaccharides
[0024] The compositions according to the invention comprise a therapeutically effective
amount of oligosaccharides, preferably acid oligosaccharides and/or neutral oligosaccharides
as described below.
[0025] Acid oligosaccharides comprise at least one acidic group while neutral oligosaccharides
do not have such an acidic group. Dietary fibers have been extensively investigated
for their health-beneficial effects. Some fibers are insoluble and non-fermentable
and pass unchanged through the gut. Other fiber types may serve as prebiotics, i.e.,
they are used by gut bacteria and stimulate their growth. Thus, fibers such as inulin
or oligosaccharides such as galactooligosaccharides (GOS) and fructo-oligosaccharides
(FOS) have been documented to stimulate growth of bifidobacteria and lactic acid bacteria,
which are important for a healthy gut flora.
Acid oligosaccharides
[0026] The term "acid oligosaccharide(s)" refers to oligosaccharides comprising at least
one acidic group selected from the group consisting of N-acetylueuraminic acid, N-glycoloylneuraminic
acid, free or esterified carboxylic acid, sulfuric acid group and phosphoric acid
group. In one embodiment the acid oligosaccharide preferably is a polyhexose. Preferably,
at least one of the aforementioned acid groups is situated at the terminal hexose
unit of the acid oligosaccharide. Preferably the acid oligosaccharide has the structure
as depicted in Fig.1, wherein the terminal hexose (left) preferably comprises a double
bond. Preferably the acid oligosaccharide contains a carboxylic acid at the terminal
hexose unit, wherein said carboxylic acid group may be free or esterified. Methods
for the manufacture of esterified pectin hydrolysates that can be suitably used in
the present uses and compositions are provided in
WO 01/60378 and/or
WO 02/42484.
[0027] The hexose units other than the terminal hexose unit(s) are preferably uronic acid
units, even more preferably galacturonic acid units. The carboxylic acid groups on
these units may be free or (partly) esterified, and preferably at least 10% is methylated
(see below).
wherein:
R is preferably selected from the group consisting of hydrogen, hydroxy or acid group,
preferably hydroxy; and
at least one selected from the group consisting of R2, R3, R4 and R5 represents N-acetylneuraminic acid, N-glycoloylneuraminic acid, free or esterified
carboxylic acid, sulfuric acid group and phosphoric acid group, and the remaining
of R2, R3, R4 and R5 representing hydroxy and/or hydrogen. Preferably one selected from the group consisting
of R2, R3, R4 and R5 represents N-acetylneuraminic acid, N-glycoloylneuraminic acid, free or esterified
carboxylic acid, sulfuric acid group or phosphoric acid group, and the remaining represent
hydroxy and/or hydrogen. Even more preferably one selected from the group consisting
of R2, R3, R4 and R5 represents free or esterified carboxylic acid and the remaining of R2, R3, R4 and R5 representing hydroxy and/or hydrogen; and
n is an integer and refers to a number of hexose units (see also Degree of Polymerisation,
below), which may be any hexose unit. Suitably n is an integer between 1-5000. Preferably
the hexose unit(s) is an uronic acid unit.
Most preferably R
1, R
2 and R
3 represent hydroxy, R
4 represent hydrogen, R
5 represents carboxylic acid, n is any number between 1 and 250, preferably between
1 and 10 and the hexose unit is galacturonic acid.
[0028] The detection, measurement and analysis of the acid oligosaccharides as used in the
present method are given in applicant's earlier patent application relating to acid
oligosaccharides, i.e.
WO 01/60378.
[0029] Preferably, the acid oligosaccharide has one, preferably two, terminal uronic acid
units, which may be free or esterified. Preferably the terminal uronic acid unit is
selected from the group consisting of galacturonic acid, glucuronic acid, guluronic
acid, iduronic acid, mannuronic acid, riburonic acid and alturonic acid. These units
may be free or esterified. In one embodiment, the terminal hexose unit has a double
bond, which is preferably situated between the C
4 and C
5 position of the terminal hexose unit. Preferably one of the terminal hexose units
comprises the double bond. The terminal hexose (e.g. uronic acid) preferably has a
structure according to Fig.2.
wherein;
R is preferably selected from the group consisting of hydrogen, hydroxy or acid group,
preferably hydroxy (see above); and
at least one selected from the group consisting of R2, R3, R4 and R5 represents N-acetylneuraminic acid, N-glycoloylneuraminic acid, free or esterified
carboxylic acid, sulfuric acid group and phosphoric acid group, and the remaining
of R2, R3, R4 and R5 representing hydroxy and/or hydrogen. Preferably one selected from the group consisting
of R2, R3, R4 and R5 represents N-acetylneuraminic acid, N-glycoloylneuraminic acid, free or esterified
carboxylic acid, sulfuric acid group and phosphoric acid group, and the remaining
of R2, R3, R4 and R5 represent hydroxy and/or hydrogen. Even more preferably one selected from the group
consisting of R2, R3, R4 and R5 represents free or esterified carboxylic acid and the remaining of R2, R3, R4 and R5 represent hydroxy and/or hydrogen; and n is an integer and refers to a number of
hexose units (see also Degree of Polymerisation, below), which may be any hexose unit.
Suitably n is an integer between 1-5000 representing the number of hexose units, said
hexose units preferably being uronic acid, even more preferably being galacturonic
acid units. The carboxylic acid groups on these units may be free or (partly) esterified,
and are preferably at least partly methylated.
Most preferably, R
2 and R
3 represent hydroxy, R
4 represent hydrogen and R
5 represents free or esterified carboxylic acid.
[0030] In one embodiment the compositions comprise a single type of acid oligosaccharide
(having a uniform degree of polymerization), while in another embodiment the compositions
comprise a mixture of acid oligosaccharides that have different Degrees of Polymerization
(DP) and/or comprise both unsaturated and saturated terminal hexose unit. Preferably
at least 5%, more preferably at least 10%, even more preferably at least 25% of the
terminal hexose units of the acid oligosaccharide unsaturated hexose unit (see e.g.
Fig.2). As each individual acid oligosaccharide preferably comprises only one unsaturated
terminal hexose unit, preferably no more than 50% of the terminal hexose units is
an unsaturated hexose unit (i.e. comprises a double bond).
A mixture of acid oligosaccharides preferably contains between 2 and 50% unsaturated
hexose units based on the total amount of hexose units, preferably between 10 and
40%.
[0031] The acid oligosaccharide as used in the present method has a degree of polymerisation
(DP) between 1 and 5000, preferably between 1 and 1000, more preferably between 2
and 250, even more preferably between 2 and 50, most preferably between 2 and 10.
If a mixture of acid oligosaccharides with different degrees of polymerisation is
used, the average DP of the acid oligosaccharide mixture is preferably between 2 and
1000, more preferably between 3 and 250, even more preferably between 3 and 50. See
also Fig.1, wherein the sum of "n" and the terminal unit (i.e. n+1) represents the
degree of polymerisation. It was found that a lower DP of the oligosaccharides improves
the palatability and results in a reduced viscosity product if the acid oligosaccharide
is administered in liquid form. The acid oligosaccharide may be a homogeneous or heterogeneous
carbohydrate.
[0032] The acid oligosaccharides used in the invention are preferably prepared from pectin,
pectate, alginate, chondroitine, hyaluronic acids, heparine, heparane, bacterial carbohydrates,
sialoglycans, fucoidan, fucooligosaccharides or carrageenan, preferably from pectin
and/or alginate. The acid oligosaccharides may be prepared by the methods described
in
WO 01/60378, e.g. chemical or enzymatic hydrolysis or partial hydrolysis, see page 8 and 9, which
is hereby incorporated by reference.
[0033] Alginates are linear unbranched polymers containing β-(1→ 4)-linked D-mannuronic
acid and α-(1→ 4)-linked L-guluronic acid residues with a wide range of average molecular
weights (100 - 100000 residues). Suitable sources of alginate include seaweeds and
bacterial alginates.
[0034] Pectin is divided into two main categories: high methoxylated pectin, which is characterised
by a degree of methoxylation above 50% and low methoxylated pectin having a degree
of methoxylation below 50%. As used herein, "degree of methoxylation" (also referred
to as DE or "degree of esterification") is intended to mean the extent to which free
carboxylic acid groups contained in the polygalacturonic acid chain have been esterified
(e.g. by methylation). The present acid oligosaccharide is preferably prepared from
high methoxylated pectin.
[0035] The acid oligosaccharides are preferably characterised by a degree of methoxylation
above 20%, preferably above 50 % even more preferably above 70%. Preferably the acid
oligosaccharides have a degree of methylation above 20%, preferably above 50 % even
more preferably above 70%.
[0036] The acid oligosaccharide(s) is/are preferably administered in an amount of between
about 10 mg and 100 gram per day, preferably between about 100 mg and 50 grams per
day, even more preferably between about 0.5 and 20 gram per day.
Neutral oligosaccharides
[0037] As mentioned above, the compositions may also comprise one or more neutral oligosaccharides,
either instead of or in addition to one or more acid oligosaccharides. One or more
neutral oligosaccharides are selected from the group consisting of cellobiose, cellodextrins,
B-cyclodextrins, indigestible dextrin, gentiooligosaccharides, glucooligosaccharides,
isomaltooligosaccharides, isomaltose, isomaltriose, panose, leucrose, palatinose,
theanderose, D-agatose, D-
lyxo-hexulose, lactosucrose, α-galactooligosaccharides, β-galactooligosaccharides, transgalactooligosaccharides,
lactulose, 4'-galatosyllactose, synthetic galactooligosaccharide, fructans - Levan-type,
fructans - Inulin-type, 1 f-β-fructofuranosylnystose, lacto N-tetraose, lacto N-neotetraose,
xylooligosaccharide, lafinose, lactosucrose and arabinooligosaccharides.
[0038] Preferably the neutral oligosaccharide is selected from the group consisting of galactooligosaccharide,
fructooligosaccharide, transgalactooligosaccharide xylooligosaccharide, lactosucrose
and arabinooligosaccharides. Even more preferably the neutral oligosaccharide is selected
from the group consisting of galactooligosaccharide, fructooligosaccharide and transgalactooligosaccharide.
[0039] Preferably the composition comprises two chemically distinct neutral oligosaccharides,
one selected from the group consisting of galactose based neutral oligosaccharide
and one selected from the group of fructose and/or glucose based oligosaccharide.
[0040] More preferably the composition comprises fructooligosaccharide and at least one
oligosaccharide selected from transgalactooligosaccharride and galactooligosaccharide.
[0041] Preferred daily amounts of neutral oligosaccharides are between about 10 mg and 100
gram per day, preferably between about 100 mg and 50 grams per day, even more preferably
between about 0.5 and 20 gram per day.
[0042] Preferably a composition comprising neutral and acid oligosaccharides is used wherein
at least 15% of the total oligosaccharides comprise of acid oligosaccharides more
preferably between 10 and 90% and most preferably between 25 and 75%. Preferably a
composition is used wherein at least 25% of the oligosaccharides are acid oligosaccharides
comprising at least one terminal uronic acid unit.
Cysteine or source of cysteine
[0043] The compositions provided comprise in addition to one or more oligosaccharides as
described above a suitable amount of cysteine and/or source of cysteine. The phrase
"source of cysteine" refers herein to all compounds that contain a biologically available
cysteine, in any form, and is calculated as the amount of cysteine amino acid that
is present in a compound, or can be derived from a compound in the body after ingestion,
on a molar basis.
[0044] Hereinbelow "cysteine equivalent" refers to an amount of cysteine as such or to an
amount of cysteine that is present in a source of cysteine. For example 100 mg NAC
(N-acetylcysteine; MW= 163.2) is equivalent to 74 mg cysteine (MW 121.15). Thus 100
mg NAC is 74 mg cysteine equivalent. Similarly this can be applied to proteins or
peptides. When a peptide (MW = xDalton) contains 3 cysteine amino acids (3yDalton),
than 100 mg of this peptide is equivalent to 100x3Y/X mg cysteine. Thus 100mg of this
peptide is 300y/x mg cysteine equivalent.
[0045] Suitable sources of cysteine according to the invention are, for example, proteins
in denatured and/or undenatured form such as milk proteins e.g. whey or casein proteins.
Egg proteins are rich in cysteine and are therefore also suitable. Plant proteins
such as pea, potato, soy and rice can also be used to provide cysteine. Also hydrolysates
of these protein sources can be used or fractions enriched for cysteine rich proteins
or peptides (e.g. as described in
EP1201137). Furthermore, synthetic cysteine equivalents, e.g. derivatives of cysteine, such
as cysteine, cysteine salts, N-acetylcysteine and/or diacetylcysteine can be used.
[0046] The HIV infected subjects are administered a daily dose of at least about 100 mg
cysteine equivalent, preferably at least about 200,400, or 600 mg cysteine equivalent
per day, more preferably at least about 1000 mg cysteine equivalent per day. It is
understood that a daily dosage can be subdivided into 2, 3 or more dosage units taken
several times a day.
[0047] In yet another embodiment the compositions according to the invention comprise one
or more compounds that stimulate glutathione levels. e.g. lipoic acid, pyruvate, oxaloacetate,
oxaloaspartate, are capable in stimulating glutathione levels. Such glutathione level
stimulating compounds may be used in addition to cysteine but also instead of cysteine.
[0048] In another embodiment the compositions comprising one or more oligosaccharides and
cysteine and/or source of cysteine further comprise one or more PUFAs and/or one or
more biologically active compounds, such as compounds found in milk or probiotic microorganisms.
Probiotic micro-organism
[0049] Probiotic micro-organism means a micro-organism which beneficially affects a HIV
patient by improving its intestinal microbial balance (
Fuller, R. J. Applied Bacteriology, 1989;66:365-378). The probiotic micro-organism may be selected from one or more microorganisms suitable
for human consumption and which is able to improve the microbial balance in the intestine.
Preferably, the present composition contains 10
4 to 10
12, more preferably from 10
5 to 10
11, most preferably from 10
7 to 5x10
10 colony forming units (cfu) of probiotic bacteria per gram uronic acid oligosaccharide
with a DP between 2 and 100. The present composition preferably contains 10
2 to 10
13 colony forming units (cfu) of probiotic bacteria per gram dry weight of the present
composition, preferably 10
4 to 10
12, more preferably 10
5 to 10
10, most preferably from 10
5 to 1x10
9 cfu. The dosage of probiotic bacteria according to the present invention is preferably
between 10
2 to 10
13, more preferably from 10
5 to 10
11, most preferably from 10
8 to 5x10
10 colony forming units (cfu) per day. Preferably live or viable bacteria are used,
but dead bacteria or bacterial fragments may also be used.
[0050] Preferably the present composition comprises bacteria of the genus Lactobacillus
and/or Bifidobacterium. Preferably the composition comprises a Bifidobacterium selected
from the group consisting of
B. longum,
B.breve and
B. bifidum and/or a Lactobacillus selected from the group consisting of
L. casei,
L paracasei, L. rhamnosus, L. acidophilus and
L. plantarum. Most preferably the present composition comprises
Bifidobacterium breve and/or
Lactobacillus paracasei.
[0051] Bifidobacterium breve is a Gram-positive, anaerobic, rod-shaped bacterium. The present
B. breve preferably has at least 95 % nucleic acid sequence identity of the 16 S rRNA sequence
when compared to the type strain of
B. breve ATCC 15700, more preferably at least 97%, 98%, 99% or more sequence identity as defined
in
Stackebrandt & Goebel, 1994, Int. J. Syst. Bacteriol. 44:846-849. Nucleic acid sequence identity is calculated for two nucleotide sequences, when
optimally aligned, using the programs GAP or BESTFIT using default parameters. The
GAP default parameters are used, with a gap creation penalty = 50 (nucleotides) /
8 (proteins) and gap extension penalty = 3 (nucleotides) / 2 (proteins). For nucleotides
the default scoring matrix used is nwsgapdna (
Henikoff & Henikoff, 1992, PNAS 89, 915-919). It is clear than when RNA sequences are said to be essentially similar or have
a certain degree of sequence identity with DNA sequences, thymine (T) in the DNA sequence
is considered equal to uracil (U) in the RNA sequence. Sequence alignments and scores
for percentage sequence identity may be determined using computer programs, such as
the GCG Wisconsin Package, Version 10.3, available from Accelrys Inc., 9685 Scranton
Road, San Diego, CA 92121-3752, USA or EMBOSSwin v. 2.10.0. The
Bifidobacterium used in the present invention preferably hybridises with the
B. breve probe and gives a signal with the 5' nuclease assay method as described in co-pending
international patent application
PCT/NL2004/000748 and european patent application
05075486.0 of the present applicant. According to a preferred embodiment, the present composition
contains at least one
B. breve selected from the group consisting of
B. breve Bb-03 (Rhodia),
B. breve M16-V (Morinaga),
B. breve R0070 (Institute Rosell, Lallemand), DSM 20091, and LMG 11613. Most preferably, the
B. breve is
B. breve M-16V (Morinaga).
In a preferred embodiment the present composition comprises
Lactobacillus paracasei. Preferably the present
L. paracasei strain has at least 95%, more preferably at least 97%, 98%, 99% or more nucleic acid
sequence identity of the 16S rRNA sequence when compared to the type strain of
L. paracasei ATCC 25032 as defined above. The
Lactobacillus used in the present invention preferably hybridises with the
L. paracasei probe and gives a signal with the 5' nuclease assay method as described in co-pending
european patent application
05075486.0 of the present applicant. According to a preferred embodiment, the present composition
contains at least a
L.
paracasei selected from the group consisting of
L. paracasei F19 (Arla, Sweden),
L. paracasei LAFTI L26 (DSM Food Specialties, the Netherlands) and
L. paracasei CRL 431 (Chr. Hansen, Denmark), LMG 12165 and LMG 11407.
Polyunsaturated fatty acids:
[0052] The present inventors found that eicosapentaenoic acid (EPA, n-3) and gamma linolenic
acid (GLA, n-6) effectively reduce inflammatory mediated intestinal tight junction
permeability. Hence a composition, suitable for improving intestinal barrier integrity
is provided, which comprises (in addition to oligosaccharides and cysteine and/or
source of cysteine) EPA and/or GLA. Based on the biochemical pathways it can be hypothesized
that also other combinations of fatty acids are also effective. Thus, compositions
comprising one or more other PUFAs or mixtures thereof are also provided. For example
a mixture of any of EPA, docosahexaenoic acid (DHA, n-3), dihomo-gamma linolenic acid
(DGLA, C20:3n-6), stearidonic acid (STA, C18:4n-4), alpha linolenic acid (ALA, C18:3n-3),
(docosapentaenoic acid (DPA, C22:5n-3), eicosatetranoic acid (C20:4n-3) and/or arachidonic
acid (AA, n-6) may be used.
[0053] Suitably a relatively high daily dose of the polyunsaturated fatty acids is used.
In one embodiment at least about 25 en%, preferably at least about 30 en%, more preferably
at least about 35 en% of a fat blend comprising n-3 and/or n-6 fatty acids is used
(en% is short for energy percentage and represents the relative amount each constituent
contributes to the total caloric value of the preparation). Preferred daily amounts
are at least 1 gram PUFA, more preferably between 1-50 gram PUFA, more preferably
between 5 and 25 gram PUFA and most preferred is an amount between 7.5 and 15 gram
PUFA.
[0054] An optimal fat blend may e.g. comprise 40% borage oil and 60% fish oil. The n-3/n-6
fatty acid ratio is then between 1-2 and the weight percentage of n-3 is between 20-40,
and of n-6 is between 15-35 of total fatty acid content. Borage oil can partly or
completely be replaced by evening primrose oil.
[0055] Therefore preferred daily amounts are at least 0.1 gram EPA and 0.05 gram GLA, more
preferably between 0.1 and 5 gram EPA and between 0.05 and 2.5 gram GLA, more preferably
between 0.5 and 2.5 gram EPA and between 0.25 and 1.25 gram GLA and most preferred
is an amount between 0.75 and 1.5 gram EPA and between 0.37 and 0.75 gram GLA.
Biologically active ingredients
[0056] The compositions according to the invention may further comprise one or more biologically
active molecules, preferably components found naturally in milk. These include growth
factors, immunoglobulins, and other milk components or milk derived components.
A. Growth factors
[0057] It has been found that milk growth factors are beneficial for gut health. Transforming
growth factor-beta, insulin like growth factor and keratinocyte growth factors are
the most important examples of milk growth factors. Therefore, in one embodiment the
compositions further comprise one or more growth factors, e.g. about 1-500 µg growth
factors per day.
B. Immunoglobulins
[0058] Immunoglobulins have been shown to protect against intestinal infections and the
compositions according to the invention suitably comprise a daily dose from 0,1 to
10g Immunoglobulins
C. Other ingredients
[0059] Other bioactive ingredients obtainable from milk e.g. nucleotides, fatty acids, oligosaccharides
were also found to have a beneficial effect on the gut barrier function and may therefore
be suitably used in the manufacture of the compositions.
D. Colostrum
[0060] In one embodiment the compositions comprise Colostrum. Colostrum is the pre-milk
fluid secreted by the mammary glands of mammalian mothers after giving birth, in particular
cows after calving. Colostrum contains many biologically active milk ingredients and
is therefore an excellent source of biologically active molecules. Colostrum, being
a protein source, has the additional advantage of providing cysteine. For having beneficial
effects in HIV patients at least about 5 gram colostrum are provided on a daily basis,
preferably at least about 10 gram, more preferably at least about 20 g per day or
more.
[0061] Extracts from milk proteins, such as a whey growth factor extract as described in
EP0545946 or a casein extract as described in
WO02083164, immunoglobulin concentrates, lactoferrin or other concentrated whey fractions can
also be used to improve the gut barrier function of HIV patients.
[0062] It is understood that the biologically active molecules or components may be obtained
using a range of methods. Many are commercially available, or can be made synthetically,
by recombinant DNA technology or they can be (partially) purified or extracted from
natural sources such as milk. Also mixtures of any of the biologically active molecules
or components comprising these molecules may be used.
Compositions suitable for blocking DC-sign receptors
[0063] In another embodiment compositions suitable for the treatment of DC-sign mediated
diseases, such as HIV or AIDS, are provided. Such compositions comprise a suitable
amount of oligosaccharides, especially acid oligosaccharides as described hereinabove
and in Example 1. Preferred are oligosaccharides which have a IC50 value of about
1000, 600, 400, more preferably 200µg/ml or less, such as 150, 100, 50, 25 µg/ml or
less. The IC 50 value can be determined using methods known in the art (see Examples
1).
[0064] These compositions additionally further comprise cysteine and/or source of cysteine,
and at least 25 en% of a fat blend comprising n-3 and n-6 fatty acids as described
elsewhere herein. The oligosaccharides may be formulated as a, pharmaceutical composition
or as a food or food supplement composition (as described herein below for compositions
comprising oligosaccharides and cysteine and/or source of cysteine.
Nutritional compositions and food supplements
[0066] It was found that the oligosaccharides and cysteine and/or source of cysteine can
be advantageously applied in food, such as baby food and clinical food. Such food
preferably comprises lipid, protein and carbohydrate and can be administered in a
liquid or solid form. The term "liquid food" as used in the present invention includes
dry food (e.g. powders) that are accompanied with instructions as to admix said dry
food mixture with a suitable liquid (e.g. water). Solid food includes food in the
form of a supplement bar with a water activity between 0.2 and 0.4. Water activity
can be defined as the ratio of the water vapour pressure of a product to the vapour
pressure of pure water at the same temperature. The solid product must meet target
water activity otherwise the product will not be shelf stable. Also semi-solid food
and food-supplements are provided.
[0067] Hence, the present invention also relates to a nutritional composition that in addition
to the present oligosaccharides and cysteine and/or source of cysteine preferably
comprises between 5 and 50 en% lipid, between 10 and 60 en% protein, between 15 and
85 en% carbohydrate according to the claims. In the context of this invention it is
to be understood that the oligosaccharides in the compositions of the present invention
do not deliver calories and are therefore not included in the en% mentioned herein.
All proteins, peptides, amino acids do contribute calories and therefore are included
in the en% mentioned herein. In one embodiment the nutritional composition comprises
between 15 and 50 en% lipid, between 25 and 60 en% protein and between 15 and 45 en%
carbohydrate. In another embodiment the present nutritional composition comprises
between 15 and 50 en% lipid, between 35 and 60 en% protein and between 15 and 45 en%
carbohydrate.
[0068] Preferably lipids are used that have a high content of EPA or GLA. Fish oil and borage
or evening primrose oil are preferred sources of these polyunsaturated fatty acids.
[0069] A source of digestible carbohydrate may be added to the nutritional formula. It preferably
provides about 25% to about 40% of the energy of the nutritional composition. Any
suitable (source of) carbohydrate may be used, for example sucrose, lactose, glucose,
fructose, corn syrup solids, and maltodextrins, and mixtures thereof.
[0070] Preferably vitamins and minerals are present in amounts as required by FSMP regulations.
[0071] Diarrhea is a major problem in many HIV patients that receive liquid foods. It was
found that stool problems are reduced by administering the present oligosaccharides
in a dry nutritional composition or in liquid nutritional composition which have an
osmolality between 50 and 500 mOsm/kg, more preferably between 100 and 400 mOsm/kg.
[0072] In view of the above, the nutritional composition preferably does not deliver excessive
calories. Hence, the nutritional composition preferably does not contain more that
500 kcal/daily dose, more preferably between 200 and 400 kcal/daily dose and more
preferably between 250 and 350 kcal/daily dose.
[0073] In accordance with the foregoing, the present invention relates to a nutritional
composition according to the claims.
[0074] Also disclosed is a food composition comprising between 15 and 50 en% lipid, between
35 and 60 en% protein, between 15 and 45 en% carbohydrate, acid oligosaccharide and
neutral oligosaccharide and cysteine or and/or source of cysteine wherein the source
of cysteine is selected from the group consisting of NAC, colostrum, egg proteins
or combinations thereof.
[0075] The nutritional composition is preferably in the form of or administered as a food
supplement. This nutritional composition or food supplement can be advantageously
used in a method for treating HIV patients, said method comprising administering said
composition or supplement to a mammal, preferably a human infected with HIV.
[0076] Also provided is a method for manufacturing a composition for use in the treatment
of HIV, said method comprising
- providing a suitable amount of one or more oligosaccharides;
- providing a suitable amount of cysteine and/or source of cysteine
- formulating both of the above components into a suitable food or food supplement or
pharmaceutical composition.
[0077] The following examples illustrate the invention. Unless stated otherwise, the practice
of the invention will employ standard conventional methods of molecular biology, pharmacology,
immunology, virology, microbiology or biochemistry. Such techniques are described
in
Sambrook and Russell (2001) Molecular Cloning: A Laboratory Manual, Third Edition,
Cold Spring Harbor Laboratory Press, NY, in
Volumes 1 and 2 of Ausubel et al. (1994) Current Protocols in Molecular Biology, Current
Protocols, USA and
Remington's Pharmaceutical Sciences, Mack Publishing Company, Philadelphia, Pa., 17th
ed. (1985),
Microbiology: A Laboratory Manual (6th Edition) by James Cappuccino,
Laboratory Methods in Food Microbiology (3rd edition) by W. Harrigan (Author) Academic
Press.
EXAMPLES
Example 1. Blockage of DC-SIGN - Fc binding by acid oligo's and GOS
[0078] Blocking DC=SIGN has been shown to prevent viral translocation from dendritic cells
to CD4 T-cells. The inventors surprisingly found that oligosaccharides can block DC-SIGN
with different efficacy. Acid oligosaccharides (AOS), like pectin hydrolysate, are
the most potent as shown in Table 1. These results show that AOS can prevent binding
of Fc fragments to DC-SIGN at the lowest concentration.
TABLE 1. EFFICACY OF DC-sign BINDING BY OLIGOSACCHARIDES
Oligosaccharide |
I.C. 50 (µg/ml) |
Acid Oligosaccharide (pectin hydrolysate) |
200 |
Galacto oligosaccharides (Trans galacto-oligosaccharides) |
600 |
Fructooligosaccharide (Inuline HP) |
>1000 |
Material and methods:
[0079] Oligosaccharide preparations were coated on ELISA plate in serial dilutions. DC-SIGN
- Fc binding was measured in an ELISA using anti-DC-SIGN- Fc and was visualized by
adding a labeled secondary antibody. OD was measured with a spectrophotometer (Becton
Dickinson) after 20 minutes of incubation. Results are depicted as the inhibitory
concentration at 50% inhibition.
Example 2. Composition of a nutritional bar
[0080]
Raw Material |
Code |
g/ day |
protein |
g/ 100g |
Colostrum |
SR |
20.00 |
15.00 |
27.38 |
borage oil (Ropufa 25 n-6) |
2000342 |
4.00 |
0.00 |
5.48 |
EPA-DHA oil (Maruha) |
2001292 |
6.00 |
0.00 |
8.21 |
Galacto-oligosaccharides Elix'or syrup |
2001189 |
15.38 |
0.00 |
21.06 |
Inuline (Raftiline HP) |
2001190 |
0.79 |
0.00 |
1.08 |
Acid Oligos (pectin hydrol.) |
SR |
8.54 |
0.11 |
11.69 |
N-acetyl-Cysteine |
SR |
1.83 |
1.34 |
2.50 |
Fructosestroop |
JJ |
13.20 |
0.00 |
18.07 |
Glycerine |
JJ |
3.30 |
0.00 |
4.52 |
|
|
|
|
|
|
per day kcal |
En% |
|
|
energy protein |
66 |
26.9 |
|
|
energy carbohydrates |
82 |
33.4 |
|
|
energy fat |
97 |
39.7 |
|
|
|
245 |
|
|
|
Example 3. Composition of a nutritional bar
[0081]
Raw Material |
Code |
g/ day |
protein |
carbs |
fat |
g/ 100g |
Colostrum |
SR |
20.00 |
15.00 |
2.10 |
0.80 |
21.04 |
borage olie (Ropufa 25 n-6) |
2000342 |
4.00 |
0.00 |
0.00 |
4.00 |
4.21 |
EPA-DHA oil (Maruha) |
2001292 |
6.00 |
0.00 |
0.00 |
6.00 |
6.31 |
Galacto-oligosaccharides (Elixer or syrup) |
2001189 |
15.38 |
0.00 |
4.78 |
0.00 |
16.18 |
Inuline (Raftiline HP) |
2001190 |
0.79 |
0.00 |
0.00 |
0.00 |
0.83 |
Acid Oligos (pectin hydrol.) |
SR |
8.54 |
0.11 |
0.09 |
0.00 |
8.98 |
Egg shell membrane powder |
|
21.09 |
16.87 |
0.00 |
0.00 |
22.19 |
Fructosestroop |
JJ |
15.40 |
0.00 |
11.92 |
0.00 |
16.20 |
glycerine |
JJ |
3.85 |
0.00 |
3.83 |
0.00 |
4.05 |
|
|
|
|
|
|
|
SUM |
|
95.05 |
31.98 |
22.72 |
10.80 |
100.00 |
|
|
|
|
|
|
|
|
per day kcal |
En% |
per 100g kcal |
|
|
|
energy protein |
128 |
40.5 |
135 |
|
|
|
energy carbs |
91 |
28.8 |
96 |
|
|
|
energy fat |
97 |
30.8 |
102 |
|
|
|
SUM |
316 |
|
332 |
|
|
|
Example 4. Powder composition
[0082]
Raw Material |
Code |
g/ day |
protein |
carbs |
fat |
g/ 100g |
Colostrum |
SR |
20.00 |
15.00 |
2.10 |
0.80 |
29.39 |
borage oil (Ropufa 25 n-6) |
2000342 |
4.00 |
0.00 |
0.00 |
4.00 |
5.88 |
EPA-DHA oil (Maruha) |
2001292 |
6.00 |
0.00 |
0.00 |
6.00 |
8.82 |
GOS%MD DE2 powder |
2001189 |
14.78 |
0.00 |
7.66 |
0.00 |
21.72 |
Inuline (Raftiline HP) |
2001190 |
0.79 |
0.00 |
0.00 |
0.00 |
1.16 |
Acid Oligos (pectin hydrol.) |
SR |
8.54 |
0.11 |
0.09 |
0.00 |
12.55 |
N-acetyl-Cysteine |
SR |
1.83 |
1.34 |
0.00 |
0.00 |
2.69 |
MD DE47 |
MM |
7.00 |
0.01 |
6.75 |
0.02 |
10.29 |
MD DE47 |
MM |
5.00 |
0.01 |
4.82 |
0.01 |
7.35 |
SSL (emulsifier) |
SHS |
0.11 |
0.00 |
0.00 |
0.11 |
0.17 |
|
|
|
|
|
|
|
SUM |
|
68.05 |
16.46 |
21.41 |
10.94 |
100.0 |
|
|
|
|
|
|
|
|
per day kcal |
En% |
per 100g kcal |
|
|
|
energy protein |
66 |
26.3 |
97 |
|
|
|
energy carbs |
86 |
34.3 |
126 |
|
|
|
energy fat |
98 |
39.4 |
145 |
|
|
|
SUM |
250 |
|
367 |
|
|
|
Example 5. Powder composition
[0083]
Raw Material |
Code |
g/ day |
protein |
carbs |
fat |
g/ 100g |
Colostrum |
SR |
20.00 |
15.00 |
2.10 |
0:80 |
19.95 |
borage oil (Ropufa 25 n-6) |
2000342 |
4.00 |
0.00 |
0.00 |
4.00 |
3.99 |
EPA-DHA oil (Maruha) |
2001292 |
6.00 |
0.00 |
0.00 |
6.00 |
5.98 |
GOS/MaltoDex |
2001189 |
14.78 |
0.00 |
7.66 |
0.00 |
14.74 |
(DE2 powder) |
|
|
|
|
|
|
Inuline (Raftiline HP) |
2001190 |
0.79 |
0.00 |
0.00 |
0.00 |
0.79 |
Acid Oligos (pectin hydrol.) |
SR |
8.54 |
0.11 |
0.09 |
0.00 |
8.52 |
alpha-lactalbumin (Davisco) |
|
34.03 |
31.21 |
0.17 |
0.17 |
33.94 |
MaltoDex DE47 |
MM |
7.00 |
0.01 |
6.75 |
0.02 |
6.98 |
MaltoDex DE47 |
MM |
5.00 |
0.01 |
4.82 |
0.01 |
4.99 |
SSL (emulsifier) |
SHS |
0.11 |
0.00 |
0.00 |
0.11 |
0.11 |
|
|
|
|
|
|
|
SUM |
|
100.25 |
46.33 |
21.58 |
11.11 |
100.00 |
|
|
|
|
|
|
|
|
per day kcal |
En% |
per 100g kcal |
|
|
|
energy protein |
185 |
49.9 |
185 |
|
|
|
energy carbs |
86 |
23.2 |
86 |
|
|
|
energy fat |
100 |
26.9 |
100 |
|
|
|
SUM |
372 |
|
371 |
|
|
|
Example 6. Liquid nutritional composition
[0084]
Raw Material |
Code |
g/ day |
protein |
carbs |
fat |
g/ ltr |
borage oil (Ropufa 25 n-6) |
2000342 |
4.00 |
0.00 |
0.00 |
4.00 |
10.67 |
EPA-DHA oil (Maruha) |
2001292 |
6.00 |
0.00 |
0.00 |
6.00 |
16.00 |
Galacto-oligosacchariden |
2001189 |
15.38 |
0.00 |
4.78 |
0.00 |
41.01 |
(Elixer or syrup) |
|
|
|
|
|
|
Inuline (Raftiline HP) |
2001190 |
0.79 |
0.00 |
0.00 |
0.00 |
2.11 |
Acid Oligosaccharides |
SR |
8.54 |
0.11 |
0.09 |
0.00 |
22.77 |
(pectin hydrolysate) |
|
|
|
|
|
|
Egg shell membrane powder |
SR |
21.09 |
16.87 |
0.00 |
0.00 |
56.24 |
WPH (cysteine peptide) |
SR |
|
0.00 |
0.00 |
0.00 |
0.00 |
MaltoDextrin (DE47) |
MM |
18.80 |
0.02 |
18.12 |
0.05 |
50.13 |
|
|
|
|
|
|
|
SUM |
|
74.60 |
17.00 |
22.99 |
10.05 |
198.93 |
|
|
|
|
|
|
|
|
per day kcal |
En% |
per ltr kcal |
|
|
|
energy protein |
68 |
27.2 |
181 |
|
|
|
energy carbs |
92 |
36.7 |
245 |
|
|
|
energy fat |
90 |
36.1 |
241 |
|
|
|
SUM |
250 |
|
668 |
|
|
|
Example 7. Liquid nutritional composition
[0085]
Raw Material |
Code |
g/ day |
protein |
carbs |
fat |
g/ ltr |
borage olie Ropufa 25 n-6 |
2000342 |
4.00 |
0.00 |
0.00 |
4.00 |
10.67 |
Maruha EPA-DHA oil |
2001292 |
6.00 |
0.00 |
0.00 |
6.00 |
16.00 |
Galacto-oligosacchariden (Elixer or syrup) |
2001189 |
15.38 |
0.00 |
4.78 |
0.00 |
41.01 |
Raftiline HP (Inuline) |
2001190 |
0.79 |
0.00 |
0.00 |
0.00 |
2.11 |
AOS (pectin hydrolysate) |
SR |
8.54 |
0.11 |
0.09 |
0.00 |
22.77 |
WPH (cysteine peptide) |
SR |
24.19 |
20.83 |
0.92 |
0.02 |
64.51 |
MDDE47 |
MM |
13.50 |
0.02 |
13.01 |
0.03 |
36.00 |
|
|
|
|
|
|
|
SUM |
|
72.40 |
20.95 |
18.80 |
10.06 |
193.07 |
|
|
|
|
|
|
|
|
per day kcal |
En% |
per ltr kcal |
|
|
|
energy protein |
84 |
33.6 |
223 |
|
|
|
energy carbs |
75 |
30.1 |
201 |
|
|
|
energy fat |
91 |
36.3 |
241 |
|
|
|
SUM |
250 |
|
665 |
|
|
|
1. Use of one or more acid and neutral oligosaccharides and of cysteine and/or source
of cysteine, in the manufacture of a composition for the treatment of HIV or AIDS
in a mammal, said composition comprising a therapeutically effective amount of acid
and neutral oligosaccharides wherein the acid oligosaccharides are prepared from pectin,
pectate, alginate, chondroitine, hyaluronic acids, heparine, heparane, sialoglycans,
fucoidan, fucooligosaccharides or carrageenan and the neutral oligosaccharide is selected
from the group consisting of galactooligosaccharide, fructooligosaccharide, transgalactooligosaccharide
xylooligo-saccharide, lactosucrose and arabinooligosaccharides, and wherein said source
of cysteine is selected from N-acetylcysteine, whey, colostrum, egg proteins or a
combination thereof, and wherein the cysteine and/or source of cysteine provide at
least 100 mg cysteine equivalent in a daily dose.
2. Use according to the preceding claim wherein the cysteine and/or source of cysteine
provide at least 600, preferably at least 1000 mg, cysteine equivalent in a daily
dose.
3. Use according to any of the preceding claims, wherein acid oligosaccharides is pectin
hydrolysate.
4. Use according to any of the preceding claims, wherein the neutral oligosaccharides
is a mixture of fructooligosaccharide and galactooligosaccharide.
5. Use according to any of the preceding claims, wherein at least 15% of the total oligosaccharides
comprise acid oligosaccharides.
6. Use according to any of the preceding claims, wherein the composition further comprises
polyunsaturated fatty acids (PUFA).
7. Use according to claim 6 wherein the PUFA comprises at least 20% GLA plus EPA, based
on the total fatty acid content.
8. A food composition comprising between 15 and 50 en% lipid, between 25 and 60 en% protein,
between 15 and 45 en% carbohydrate, acid oligosaccharide prepared from pectin, pectate,
alginate, chondroitine, hyaluronic acids, heparine, heparane, sialoglycans, fucoidan,
fucooligosaccharides or carrageenan, preferably pectin hydrolysate and neutral oligosaccharide
selected from the group consisting of galactooligosaccharide, fructooligosaccharide,
transgalactooligosaccharide, xylooligo-saccharide, lactosucrose and arabinooligosaccharides,
and cysteine and/or source of cysteine selected from N-acetylcysteine, whey, colostrum,
egg proteins or combinations thereof, wherein the composition comprises at least 25
en% of a fat blend comprising n-3 and n-6 fatty acids.
9. A food composition comprising between 15 and 50 en% lipid, between 35 and 60 en% protein,
between 15 and 45 en% carbohydrate, acid oligosaccharide prepared from pectin, pectate,
alginate, chondroitine, hyaluronic acids, heparine, heparane, sialoglycans, fucoidan,
fucooligosaccharides or carrageenan, preferably pectin hydrolysate and neutral oligosaccharide
selected from the group consisting of galactooligosaccharide, fructooligosaccharide,
transgalactooligosaccharide, xylooligo-saccharide, lactosucrose and arabinooligosaccharides,
and cysteine and/or source of cysteine selected from N-acetylcysteine, whey, colostrum,
egg proteins or combinations thereof, wherein the composition comprises at least 25
en% of a fat blend comprising n-3 and n-6 fatty acids.
1. Verwendung von einem oder mehreren sauren und neutralen Oligosacchariden und von Cystein
und/oder einem Ausgangsmaterial von Cystein bei der Herstellung einer Zusammensetzung
für die Behandlung und/oder Verhütung von HIV oder AIDS in einem Säuger, wobei die
Zusammensetzung eine therapeutisch wirksame Menge von sauren und neutralen Oligosacchariden
umfasst, wobei die sauren Oligosaccharide aus Pectin, Pectat, Alginat, Chondroitin,
Hyaluronsäuren, Heparin, Heparan, Sialoglycanen, Fucoidan, Fucooligosacchariden oder
Carrageen hergestellt werden und das neutrale Oligosaccharid ausgewählt ist aus der
Gruppe bestehend aus Galactooligosaccharid, Fructooligosaccharid, Transgalactooligosaccharid,
Xylooligosaccharid, Lactosucrose und Arabinooligosacchariden, und wobei das Ausgangsmaterial
von Cystein ausgewählt ist aus N-Acetylcystein, Molke, Kolostrum, Eiproteinen oder
einer Kombination davon, und wobei das Cystein und/oder Ausgangsmaterial von Cystein
wenigstens 100 mg Cysteinäquivalent in einer Tagesdosis bereitstellen.
2. Verwendung nach Anspruch 1, wobei das Cystein und/oder Ausgangsmaterial von Cystein
wenigstens 600, vorzugsweise wenigstens 1000 mg Cysteinäquivalent in einer Tagesdosis
bereitstellen.
3. Verwendung nach einem der vorangehenden Ansprüche, wobei es sich bei sauren Oligosacchariden
um Pectinhydrolysat handelt.
4. Verwendung nach einem der vorangehenden Ansprüche, wobei es sich bei den neutralen
Oligosacchariden um eine Mischung von Fructooligosaccharid und Galactooligosaccharid
handelt.
5. Verwendung nach einem der vorangehenden Ansprüche, wobei wenigstens 15 % der gesamten
Oligosaccharide saure Oligosaccharide umfassen.
6. Verwendung nach einem der vorangehenden Ansprüche, wobei die Zusammensetzung außerdem
mehrfach ungesättigte Fettsäuren (PUFA) umfasst.
7. Verwendung nach Anspruch 6, wobei die PUFA wenigstens 20 % GLA plus EPA, bezogen auf
den Gesamtfettsäuregehalt, umfasst.
8. Nahrungsmittelzusammensetzung umfassend zwischen 15 und 50 en% Lipid, zwischen 25
und 60 en% Protein, zwischen 15 und 45 en% Kohlenhydrat, saures Oligosaccharid, hergestellt
aus Pectin, Pectat, Alginat, Chondroitin, Hyaluronsäuren, Heparin, Heparan, Sialoglycanen,
Fucoidan, Fucooligosacchariden oder Carrageen, vorzugsweise Pectinhydrolysat, und
neutrales Oligosaccharid, ausgewählt aus der Gruppe bestehend aus Galactooligosaccharid,
Fructooligosaccharid, Transgalactooligosaccharid, Xylooligosaccharid, Lactosucrose
und Arabinooligosacchariden, und Cystein und/oder ein Ausgangsmaterial von Cystein
ausgewählt aus N-Acetylcystein, Molke, Kolostrum, Eiproteinen oder Kombinationen davon,
wobei der Zusammensetzung mindestens 25 en% einer Fettmischung umfassend n-3 und n-6
Fettsäuren umfasst.
9. Nahrungsmittelzusammensetzung umfassend zwischen 15 und 50 en% Lipid, zwischen 35
und 60 en% Protein, zwischen 15 und 45 en% Kohlenhydrat, saures Oligosaccharid, hergestellt
aus Pectin, Pectat, Alginat, Chondroitin, Hyaluronsäuren, Heparin, Heparan, Sialoglycanen,
Fucoidan, Fucooligosacchariden oder Carrageen, vorzugsweise Pectinhydrolysat, und
neutrales Oligosaccharid, ausgewählt aus der Gruppe bestehend aus Galactooligosaccharid,
Fructooligosaccharid, Transgalactooligosaccharid, Xylooligosaccharid, Lactosucrose
und Arabinooligosacchariden, und Cystein und/oder ein Ausgangsmaterial von Cystein
ausgewählt aus N-Acetylcystein, Molke, Kolostrum, Eiproteinen oder Kombinationen davon,
wobei der Zusammensetzung mindestens 25 en% einer Fettmischung umfassend n-3 und n-6
Fettsäuren umfasst.
1. Utilisation d'un ou plusieurs oligosaccharides acides et neutres et de cystéine et/ou
de source de cystéine dans la fabrication d'une composition pour le traitement et/ou
la prévention du VIH ou du SIDA chez un mammifère, ladite composition comprenant une
quantité efficace sur le plan thérapeutique d'oligosaccharides acides et neutres,
les oligosaccharides acides étant préparés à partir de pectine, de pectate, d'alginate,
de chondroïtine, d'acides hyaluroniques, d'héparine, d'héparane, de sialoglycanes,
de fucoïdane, de fuco-oligosaccharides ou de carraghénane, et l'oligosaccharide neutre
étant sélectionné dans le groupe constitué des galacto-oligosaccharide, fructo-oligosaccharide,
transgalactooligosaccharide, xylo-oligosaccharide, lactosaccharose et arabinooligosaccharides,
et ladite source de cystéine étant sélectionnée parmi de la N-acétylcystéine, des
protéines de blé, de petit lait, d'oeuf, ou une combinaison de celles-ci, dans laquelle
la cystéine et/ou source de cystéine fournit au moins 100 mg d'équivalent cystéine
dans une dose quotidienne.
2. Utilisation selon la revendication 1, dans laquelle la cystéine et/ou source de cystéine
fournit au moins 600 mg, de préférence au moins 1000 mg, d'équivalent cystéine dans
une dose quotidienne.
3. Utilisation selon l'une quelconque des revendications précédentes, dans laquelle les
oligosaccharides acides sont un hydrolysat de pectine.
4. Utilisation selon l'une quelconque des revendications précédentes, dans laquelle les
oligosaccharides neutres sont un mélange de fructo-oligosaccharide et de galacto-oligosaccharide.
5. Utilisation selon l'une quelconque des revendications précédentes, dans laquelle au
moins 15 % du total des oligosaccharides représentent des oligosaccharides acides.
6. Utilisation selon l'une quelconque des revendications précédentes, dans laquelle la
composition comprend en outre des acides gras polyinsaturés (PUFA).
7. Utilisation selon la revendication 6, dans laquelle les PUFA comprennent au moins
20 % de GLA et d'EPA, par rapport à la quantité totale d'acides gras.
8. Composition alimentaire comprenant entre 15 et 50 % en énergie de lipides, entre 25
et 60 % en énergie de protéines, entre 15 et 45 % en énergie de glucides, un oligosaccharide
acide préparé à partir de pectine, de pectate, d'alginate, de chondroïtine, d'acides
hyaluroniques, d'héparine, d'héparane, de sialoglycanes, de fucoïdane, de fuco-oligosaccharides
ou de carraghénane, de préférence un hydrolysat de pectine, et un oligosaccharide
neutre sélectionné dans le groupe constitué des galacto-oligosaccharide, fructo-oligosaccharide,
transgalacto-oligosaccharide, xylo-oligosaccharide, lactosaccharose et arabino-oligosaccharides,
et une cystéine et/ou source de cystéine sélectionnée parmi la N-acétylcystéine, des
protéines de blé, de petit lait, d'oeuf, ou une combinaison de celles-ci, dans lequel
la composition comprend au moins 25 en% d'un mélange de matières grasses comprenant
des acides gras n-3 and n-6.
9. Composition alimentaire comprenant entre 15 et 50 % en énergie de lipides, entre 35
et 60 % en énergie de protéines, entre 15 et 45 % en énergie de glucides, un oligosaccharide
acide préparé à partir de pectine, de pectate, d'alginate, de chondroïtine, d'acides
hyaluroniques, d'héparine, d'héparane, de sialoglycanes, de fucoïdane, de fuco-oligosaccharides
ou de carraghénane, de préférence un hydrolysat de pectine, et un oligosaccharide
neutre sélectionné dans le groupe constitué des galacto-oligosaccharide, fructo-oligosaccharide,
transgalacto-oligosaccharide, xylo-oligosaccharide, lactosaccharose et arabino-oligosaccharides,
et une cystéine et/ou source de cystéine sélectionnée parmi la N-acétylcystéine, des
protéines de blé, de petit lait, d'oeuf, ou une combinaison de celles-ci, dans lequel
la composition comprend au moins 25 en% d'un mélange de matières grasses comprenant
des acides gras n-3 and n-6.